Angiotensin-converting enzyme gene polymorphism in North-west Indian children with posterior urethral valves.
OBJECTIVE
To investigate the association of angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and other risk factors with renal scarring in patients with posterior urethral valves (PUV).


METHODS
Forty consecutive patients from North-west India were treated for PUV in 1997-2004. The patients were divided into group 1 (no renal scarring, n=12) and group 2 (renal scars present, n=28) based on dimercato-succinic acid scans. ACE I/D polymorphism was determined by polymerase chain reaction in PUV patients and unrelated healthy controls (n=100).


RESULTS
Mean age at presentation was 23.7+/-37.2 months and mean follow up was 4.8+/-1.5 years. Preoperative mean serum creatinine levels for group 1 (non-scarred) and group 2 (scarred) were 1.1+/-1.6 mg/dl and 1.7+/-1.6 mg/dl, respectively. One year after treatment, the serum creatinine levels had decreased to 0.6+/-0.1 mg/dl and 0.8+/-0.3 mg/dl in group 1 and group 2, respectively. ACE genotype distribution in children with PUV was no different from that of controls. The occurrence of D allele was significantly (p=0.04) higher in patients of group 2. Multivariate logistic regression analysis showed that D allele had a significant impact on renal scar formation, introducing a 4.6-fold risk (odds ratio 4.6, 95% confidence interval 1.03-20.38, p=0.04). A highly significant correlation between the occurrence of renal scarring and presence of breakthrough urinary tract infection (odds ratio=7.5, 95% confidence interval 1.60-35.07, p=0.006) and serum creatinine at follow up (odds ratio=0.6, 95% confidence interval 0.47-0.81, p=0.03) was observed. The mean values for glomerular filtration rate (GFR) after 1 year of treatment (p=0.006) and at follow up (p=0.027) were significantly different between the patients with II genotype and ID/DD genotype. Hypertension was observed in 13 patients and proteinuria in nine patients with no significant difference between the patients having II/I D/DD genotypes.


CONCLUSIONS
The presence of D allele is associated with progression of renal scarring and reduced GFR in PUV patients.
Narasimhan
Kannan Laksmi
KL
Department of Pediatric Surgery, Post Graduate Institute of Medical Education and Research, Chandigarh UT, 160012, India.
Khullar
Madhu
M
Kaur
Balpinder
B